Depending on this ECW/Smackdown co-existence, there's a few possibilities, however, overall, I'd have to say Hardy. All of this build-up just to have MVP will win probably piss off a lot of fans as it will have been useless. To me, MVP could (and should) easily move up to the main event level once losing the belt, and like others have said, chances are he'll lose to a face and the two on Smackdown most likely to beat MVP for it are Hardy and Mysterio. Now, one of the reasons I don't see Mysterio winning it as opposed to Hardy is that if MVP drops the belt and moves up to main event status, he'll need more people to feud with and Mysterio fits that bill. Kane may very well be more active on ECW in the future than Smackdown, so the main event of Smackdown is left to Undertaker, Batista, and Mysterio as faces with Edge, MVP, and Khali (ugh) as heels with Henry and Finlay a step underneath, but Finlay could be a good feud with Hardy for the US title.
Rest assured, though, no heels will take the belt from MVP and they're definitely not going to pick Palumbo over Hardy or Mysterio.